We have recently found that all A/J mice produce substantial amounts of anti-pazophenylarsonate (anti-Ar) antibodies which share idiotypic determinants. Molecules bearing the cross-reactive idiotype (CRI) have a very narrow range of isoelectric pH. We plan to isolate this antibody fraction and determine, by amino acid sequence analysis through the first hypervariable region of the light chain, whether it is homogeneous. If so, N-terminal sequence analyses will be carried out on a number of preparations to ascertain the nature of substitutions that may occur in the first hypervariable and in nonhypervariable regions. The data may be relevent to the occurrence of somatic mutations. The reason for the appearance of the cross-reacting idiotype in A/J mice will be explored. Possibilities to be tested are: that the molecules are of high affinity and that the corresponding lymphocyte receptors therefore succeed in capturing antigen; or that a large proportion of precursor lymphocytes have anti-Ar receptors. A newly devised, apparently general method for isolating B-cells according to their receptors will be further developed and applied to the isolation of cells bearing CRI. Such cells will be used in adoptive transfer experiments and recipient mice tested for the production of homogeneous antibodies. We have shown that the immunogenicity of BALB/c myeloma proteins in BALB/c mice is greatly enhanced if the immunogen is copolymerized with IgG from an allotypically different mouse strain or with rabbit IgG. The work of others indicates that the immunized mice are able to reject the corresponding myeloma tumor. We will determine whether our immunization procedures increase immunity to the tumor, and whether immunity is cellular or humoral.